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Stress and fertility- Causality?

Your best friend may say to you "Relax and you'll get pregnant faster". This frequently noted advice is the research topic of a recent publication in the journal Human Reproduction by the investigative group LIFE Study.

The LIFE (Longitudinal Investigation of Fertility and the Environment) Study is a project designed to examine the relationship between ubiquitous environmental chemicals, lifestyle, and human fecundity and fertility. The study comprises of 501 couples recruited prior to attempting pregnancy, who were followed while attempting to become pregnant for up to 12 months of trying. Of the 501 couples recruited, 401 completed the study, and were followed as they tried to conceive. All women were between the ages of 18 to 40, were married or partnered, had stopped contraceptives for only up to 2 months and had a male partner at least 18 years old.

Salivary samples were collected the day after entry into the study and the day of their first observed menses in the study period; no other salivary samples were collected over the ensuing 12 months. The salivary samples were tested for the stress biomarkers cortisone and alpha-amylase. Couples were asked to keep a daily journal recording a variety of lifestyle questions including their stress levels and frequency of intercourse.

The study results showed that of the 401 women, 87% (347) became pregnant and 13% (54) did not. These results are most consistent with expected pregnancy rates in a fertile population; women who were parous were more likely to become pregnant. Among the 401 women, 373 (93%) completed the salivary biomarkers, and there were no differences in the two stress biomarkers over those first 2 cycles (only collected samples). Interestingly, women in this study seemed to have lower levels of stress than the general population (based on self reporting), and even those women with highest levels of alpha-amylase in this study seemed to have low-levels of stress.

Salivary alpha- amylase levels were stratified into 3 levels, and those women in the highest tertile exhibited a 29% reduction in fecundity (longer time to conception) compared with women in the lowest tertile. This reduction in fecundity translated into a 2 fold increase in infertility (RR= 2.07); probability of remaining non-pregnant jumped from 15% to 30% after 12 months for those women in the upper tertile. All women in the study had the same chance of pregnancy until month six, and the lower probability of pregnancy for women in the upper tertile was not noted until women had tried to conceive for at least 6 months. In contrast, salivary cortisol levels were not associated with prediction of infertility.

The strength of this study is that it is a prospective study assessing the association between stress markers and fertility. However, there are a number of important weaknesses to note. Firstly, an association does not imply causality-- in other words, noticing an associative relationship (higher alpha-amylase levels correlating to infertility) does not mean that factors leading to higher alpha-amylase (ie stress) cause infertility. This study only looked at 2 samplings of stress biomarkers (study entry and first menses), and markers with every menses would have provided more insight into stress trends as couples try to conceive (ie do alpha-amylase levels rise over time?). Of the couples who were not pregnant after 12 months, no diagnostic testing was done, so it could be that some of the couples had important infertility factors leading to the infertility (poor sperm parameters, tubal factor, etc.), independent of alpha-amylase levels at study entry. Lastly, it is curious that this study group appeared to have lower levels of stress (as self reported) than reported as baseline levels for general populations.

While this study is of initial interest, much more needs to be assessed to really start answering the important question of the potential interplay between lifestyle stress and infertility. It is also important to note that this study population is a fertile population, and study findings may not correlate to what may be expected for an infertile group. Lastly, this study is not designed to answer the question of stress and fertility in the context of patients who are undergoing infertility treatment.

While managing stress is an important lifestyle issue for general health, including preparedness for pregnancy, it is yet to be shown to be causing infertility. So, when your best friend tells you to "relax and then you'll get pregnant", remember that most infertility occurs due to factors which are not controllable, and that the best way to overcome infertility is to seek treatment after 6 months if you are 35 or older, or 12 months if younger than 35.

Preconception stress increases the risk of infertility: results from a couple-based prospective cohort study- the LIFE study; CD Lynch et al; Hum Reprod Vol 29, No5: 1067-1075, 2014

- Isabelle Ryan, MD

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